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A new study investigates the role of lipid transporter ratios in cardiovascular outcomes. VICTOR TORRES/Stocksy
  • Researchers recently investigated whether ratios of two lipid transporters in the blood can predict cardiovascular events.
  • The lipid transporters of interest are called apolipoprotein B (apoB) and apolipoprotein A-1 (apoB1)
  • The study found that those with the highest levels of apoB and lowest levels of apoA-1 are almost three times more likely to have a heart attack than those with lower ratios of apoB to apoA-1.
  • The researchers say that future guidelines highlighting cardiovascular risk factors should consider apoB/apoA-1 ratios.

Dyslipidemia refers to abnormal levels of cholesterol and other lipids in the blood. It is a major risk factor for cardiovascular conditions.

High levels of low-density lipoprotein cholesterol (LDL-C) have links to an increased risk of cardiovascular disease. International guidelines commonly include LDL-C levels as a risk marker for cardiovascular illnesses.

Other risk markers that can assess cardiovascular risk include high-density lipoprotein cholesterol (HDL-C), which protects against cardiovascular disease risk; and apoB, which transports LDL-C and other lipids linked to cardiovascular disease to tissues in the body. ApoA-1 transports HDL-C.

Research has shown that the ratios of both apoB and apoA-1 have links to an increased risk of heart attack and stroke.

While many studies indicate that the apoB/apoA-1 ratios can indicate cardiovascular risk, current international guidelines do not include the measurement.

In a recent study, researchers led by the Karolinska Institutet in Stockholm, Sweden, investigated the link between apoB/apoA-1 ratios and incidence of nonfatal heart attacks, strokes, and cardiovascular mortality (MACEs).

The results appear in PLOS Medicine.

“The results show that the higher the apoB/apoA-1 value, the greater the risk of myocardial infarction, stroke, and need for coronary surgery,” says Prof. Göran Walldius, senior author and professor emeritus at the Institute of Environmental Medicine, Unit of Epidemiology, Karolinska Institutet.

“The study also showed that the risk was amplified in the presence of low protective levels of apoA-1.”

Prof. Walldius and Niklas Hammar, professor emeritus at the Institute of Environmental Medicine at the Karolinska Universitet, also an author of the study, sent comments to Medical News Today.

“The apoB/apoA-1 ratio can detect those individuals who have seemingly normal or even low LDL that may not be detected by only LDL, non-HDL, or even apoB alone,” they explained.

“This may be the case in individuals with [elevated levels of tryglycerides], metabolic syndrome, diabetes, and obesity who are at risk for cardiovascular complications.”

Dr. Rigved Tadwalkar explained to MNT that “the medical community has long relied upon the use of traditional markers, such as LDL-C and HDL-C to determine the risk for incident cardiovascular disease.”

Dr. Tadwalkar is a board-certified cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, who was not involved in the study. He continued:

“[…]This study furthers the argument that there is significant additional value in checking multiple apolipoprotein subtypes when performing a lipid analysis. While many of us have already begun checking apoB levels as part of our standard evaluation in dyslipidemia, this study shows us that checking apoA-1 levels and determining the ratio supplies significant prognostic information in the form of event rates for real endpoints.”

“ApoB and apoB/apoA are not new markers,“ said Dr. Laurence Sperling, FACC, FAHA, FACP, Katz Professor in preventive cardiology and founder of the Emory Center for Heart Disease Prevention at Emory University, GA.

Dr. Sperling, who was not involved in the study, told MNT, “These findings are not surprising or novel. The long-term follow-up of this cohort is of value as cardiovascular risk factors exert risk over time — we need to think in terms of ‘cholesterol years’ much like we think about exposure over time in a smoker — i.e., pack-years.”

The researchers gathered data from the AMORIS cohort, a database containing health records including blood and urine sample analyses from individuals in Sweden between 1985–1996.

Participants were either healthy individuals who underwent routine yearly health checkups or outpatients referred for lab tests.

For the data analysis, the researchers included men and women aged between 25–84 years without a history of MACE, coronary artery bypass grafting, or percutaneous coronary intervention, which is a minimally-invasive procedure that aims to unblock clogged coronary arteries.

Altogether, the researchers analyzed data from 137,100 individuals, including information on:

  • apoB levels
  • apoA-1 levels
  • total cholesterol
  • triglycerides
  • serum glucose

As the researchers had limited information on cardiovascular risk factors, such as tobacco smoking and hypertension, they used estimates for the whole cohort based on available data from 1,466 participants who had provided this data in another study.

The researchers noted that average follow-up times were 17.8 years for the entire 30-year study period. During this time, there had been 22,473 MACEs, including 8,567 nonfatal heart attacks, 8,194 nonfatal strokes, and 5,712 cardiovascular deaths.

From their analysis, the researchers found that the higher the apoB level and the lower the apoA-1 levels were, the greater the cardiovascular risk among both men and women.

Those with the highest apoB/apoA-1 values were almost three times more likely to have a heart attack. They were also at nearly a 70% greater risk of a major cardiovascular event and almost 40% more likely to die from cardiovascular causes.

The researchers also found that the apoB/apoA-1 ratio could predict cardiovascular events as early as 20 years before they happened.

After adjusting for cholesterol, triglycerides, glucose, sex, and socioeconomic status, the results remained significant.

To explain the underlying mechanisms for their findings, the researchers say that as apoB transports cholesterol to tissues, how much of it is in the blood indicates the rate at which cholesterol reaches tissues.

As apoA-1 transports cholesterol away from tissues to the liver for excretion into the gut, its quantity in the blood, taken with that of apoB, could give doctors an understanding of how much cholesterol might build up in different tissues.

They add that apoA-1 has anti-inflammatory, antioxidative, and anti-blood-clotting effects. Also, apoA-1 stimulates nitric oxide production in the arterial wall, which has vasodilatory effects, increasing blood flow and reducing blood pressure.

“ApoB and apoA-1 are surface proteins that transport cholesterol to and from the tissues,” Dr. Tadwalkar told MNT.

“ApoB is primarily responsible for transporting the most atherogenic lipoprotein particles, where they can be deposited in the arterial wall [and] cause damage.”

“Conversely, apoA-1 has a protective role, allowing for the efflux of cholesterol particles back to the liver for further elimination, and providing antioxidative and anti-inflammatory effects. For these reasons, it makes sense from a biological standpoint that measuring the ratio of ‘the bad and the good’ would have clinical value,” he added.

“The atherosclerotic process in different arterial beds and organs develops slowly over time,” explained Prof. Walldius and Prof. Hammar.

“If there is an imbalance between pro- and anti-atherogenic functions, defined by a high apoB/apoA-1 ratio, atherosclerosis speeds up with obstructions to blood flow, risk of thrombosis, embolization, or even rupture of blood vessels that may cause serious cardiovascular complications or fatal events as shown in our present study,” they added.

The researchers conclude that scientists should agree on the cut-off values for apoB/apoA-1 ratios so that cardiovascular risk guidelines can include the measurement.

The authors outline limitations to their research. Firstly, they did not have access to all major cardiovascular risk factors for the entire cohort.

They also note that they did not have data on prescribed drugs during the measurement period. This may have reduced the strength of association between apoB/apoA-1 ratios and cardiovascular events.

“This is a good quality study performed in a large population of patients, with a reasonable proportion of women, “ said Dr. Tadwalkar. “The long follow-up period and high number of events are also strengths. While randomized controlled trials are considered the gold standard to establish causality, they can be impractical in some cases and are not always necessary to accurately demonstrate relationships.”

“The primary limitation to this study is the lack of availability of all major cardiovascular risk factors when making adjustments to the data; however, there was an attempt to offset this by using validation analyses from additional research cohorts.”

“Overall, the results remained after adjusting for common risk factors in this manner. Further, the study was done on a mostly healthy population in Scandinavia, so caution must be taken when extrapolating the results to other settings,” he added.

In conclusion, Prof. Walldius and Prof. Hammar told MNT:

“Based on our long-term study […], we suggest that apoB, apoA-1, and especially the apoB/apoA-1 ratio, should be considered in future international guidelines for patients where the usual indicators of dyslipidemia are less effective for cardiovascular risk evaluation. Early detection and treatment of dyslipidemia may prevent severe cardiovascular disease and save lives.”